The purpose of this project is to investigate the pathophysiology of the respiratory disturbance in Rett patients, to characterize the clinical and electroencephalographic parameters of seizures experienced by Rett patients, to utilize neurophysiological parameters to evaluate the evolution of this syndrome, and to evaluate the response of these patients to pharmacological treatment modalities. The research will be divided into four phases: Phase I, a baseline phase prior to treatment; Phase II, an acute treatment phase with a short-acting opiate antagonist, naloxone; Phase III, evaluation of naltrexone, an opiate antagonist, vs placebo, during a double-blind/crossover study; and, Phase IV, long-term follow-up. During these four phases, the 50- 60 Rett patients and 12 autistic control patients enrolled in Project I will be evaluated by use of neurophysiological techniques that will include (1) overnight sleep studies; (2) prolonged EEG/video monitoring, including computer-based background EEG analysis; (3) assessment of ventilatory chemosensitivity during hepoxic and hypercarbic challenges; and (4) evaluation of upper airway function by partial expiratory flow volume curves and polygraphic recordings of respiratory effort, awake and asleep. The data will be utilized to test the following hypothesis: (1) These patients have abnormal awake/behavioral control of breathing. (2) There is a dysfunction of the upper airway musculature during episodes of disorganized breathing. (3) The manifestations of the Rett syndrome, including the respiratory disturbance, are, in part, the result of an underlying disturbance or abnormality in beta-endorphins and/or opiate-receptor sensitivity. (4) Some events reported to be seizures may be episodes of disorganized breathing or stereotyped hand movements. These data will also be utilized in correlation with data obtained from other projects to provide a further characterization of the Rett syndrome, a better definition of its clinical stages, and an identification of its variants.